tbuckley/cabot-search huggingface dataset:
Intralesional therapy, limb infusion/perfusion, and immune checkpoint inhibitors as first-line therapy in surgically unresectable melanoma in-transit metastases.
Authors: Danielle K DePalo, Syeda Mahrukh Hussnain Naqvi, David W. Ollila, Tina J. Hieken, Matthew Stephen Block, Winan J. van Houdt, Michel W.J.M. Wouters, Nethanel Asher, Kristy Kummerow Broman, Zoey Duncan, Matilda Anderson, David E. Gyorki, John T. Vetto, Jane Yuet Ching Hui, Robyn P.M. Saw, Serigne N. Lo, Youngchul Kim, Alexander Christopher Jonathan Van Akkooi, Roger Olofsson Bagge, Jonathan S. Zager
Journal: Journal of Clinical Oncology (2023)

9574 Background: Surgery remains the gold standard for resectable melanoma in-transit metastases (ITM). Unresectable ITM is a heterogenous disease with multiple treatment (tx) options including systemic therapies such as immune checkpoint inhibitors (ICI), regional therapies such as isolated limb infusion or perfusion (ILI/P), and intratumoral therapies such as talimogene laherparepvec (IT). Until now, there has been no direct comparison of these first-line tx for unresectable ITM. Methods: A retrospective chart review of patients (pts) with ITM treated first-line with IT, ILI/P, or ICI was performed at 11 institutions. Pts with unresectable ITM, synchronous nodal or distant metastatic disease were excluded. Results: 560 pts (54% women) were identified, 86 received IT, 353 received ILI/P, and 121 received ICI from 1990-2022. ICI pts were youngest, IT pts were oldest (p&lt;0.001). Limb was the most common site of ITM. There was no difference in largest ITM size, but number of lesions (burden of disease (BOD)) was highest in ILI/P pts and lowest in IT pts (p=0.003). Toxicity (tox) requiring &lt;90 days (p&lt;0.001) or &gt; 90 days (p=0.034) of pharmacologic tx as well as tox requiring hospitalization (p&lt;0.001) was greatest in ICI pts. Lymphedema was more likely in ILI/P pts (p=0.016). Median follow-up was much longer for ILI/P pts at 8.0 yrs compared to 2.5 yrs for IT pts and 3.1 yrs for ICI pts. Overall response rate (ORR) was 82.2% in ILI/P pts, significantly higher than IT (72.1%, p=0.047) or ICI pts (63.6%, p&lt;0.001). Overall survival was similar between modalities (p=0.167); however, ILI/P pts had worse progression-free survival (PFS) (p&lt;0.0001) and melanoma-specific survival (MSS) (p=0.003). On multivariable analysis of MSS by number of ITM present, MSS remained worst if ILI/P was used for low BOD, ≤3 ITM (p=0.005), but no difference was seen between tx modalities for higher BOD, &gt;3 ITM (p=0.211). Conclusions: ICI was used more often in younger pts with less BOD, IT in older pts with less BOD, and ILI/P in older pts with high BOD. Short and long-term tox was greater in ICI. ILI/P had the best ORR, but ICI and IT resulted in greater overall MSS. Multidisciplinary consideration of risks and benefits of each modality should guide ITM tx selection. [Table: see text]
Impact of <i>EML4-ALK</i> fusion variant and co-occurring <i>TP53</i> mutation on treatment duration of first-line next-generation ALK TKIs in <i>ALK </i>fusion+ NSCLC.
Authors: Kaushal Parikh, Anastasios Dimou, Konstantinos Leventakos, Yin Wan, Huamao Mark Lin, Sylvie Vincent, Jennifer Elliott, Ioana R Bonta
Journal: Journal of Clinical Oncology (2023)

9029 Background: Molecular biomarkers such as EML4-ALK fusion variant 3 (V3) and TP53 mutation are associated with poor prognosis in patients (pts) with anaplastic lymphoma kinase fusion positive ( ALK+) non–small cell lung cancer (NSCLC). We evaluated the effect of EML4-ALK fusion variants and TP53 mutation status on time to treatment discontinuation (TTD) of first-line (1L) treatment with a next-generation ALK tyrosine kinase inhibitor (TKI) in pts with ALK+ NSCLC in the real-world setting. Methods: Pts with advanced/metastatic NSCLC who were ALK+ in circulating tumor DNA by Guardant360 (G360) liquid biopsy test from Jan 1, 2018, to Dec 31, 2021, and received 1L monotherapy with a next-generation ALK TKI (alectinib, brigatinib, ceritinib, lorlatinib) were identified in the Guardant INFORM clinical-genomics database. Median TTD of 1L ALK TKI treatment was determined by Kaplan-Meier (KM) methods. The impact of EML4-ALK fusion variant and TP53 mutation status on TTD was evaluated. Results: Database search identified 495 pts with advanced/metastatic NSCLC who had ALK fusion by G360; of these, 214 pts received 1L treatment with a next-generation ALK TKI; 164 had G360 testing before treatment (alectinib, n=147; brigatinib, n=7; ceritinib, n=2; lorlatinib, n=8). Among these 164 pts, median age was 58.6 y, 53% were female, and 29% had baseline brain metastases. Median follow-up from start of 1L treatment was 14.8 mo. Median TTD was 19.6 mo (95% CI: 13.6–not reached [NR]). TP53 mutations were detected in 66 pts (40%). Median (95% CI) TTD in pts with TP53 mutation vs WT was 17.1 (9.5–28.5) vs 21.9 mo (14.3–NR; log-rank P=0.1712). Of 130 pts with EML4-ALK fusion variant type detected, 63 (48%) had V1, 54 (42%) V3, 8 (6%) V2, 4 (3%) V5, and 1 (1%) V8. In pts with EML4-ALK fusion V1 vs V3, median (95% CI) TTD was 19.0 (13.6–NR) vs 21.8 mo (8.7–NR; HR: 0.73; log-rank P=0.3039), with the KM plot showing numerically longer TTD in pts with V1 vs V3 during the first 18 mo and lines crossing at the tail end. Of 117 pts with both an EML4-ALK fusion variant (V1/V3) and TP53 data, 21 (18%) had both V3 and a TP53 mutation. Pts with co-occurring EML4-ALK V3 and TP53 mutation had the shortest TTD (median TTD 8.7 [3.9–NR; HR: 2.59; P=0.0219]; Table). Conclusions: Among pts with NSCLC and ALK fusion, co-occurrence of EML4-ALK V3 and TP53 mutation is common and associated with poor prognosis and high risk of early discontinuation of 1L treatment with a next-generation ALK TKI, most likely due to disease progression. Additional novel or combination therapies are warranted for this subpopulation. [Table: see text]
Correlation of DNA methylation signatures with response to immune checkpoint inhibitors in metastatic melanoma.
Authors: Julia Maria Ressler, Erwin Tomasich, Teresa Hatziioannou, Helmut Ringl, Gerwin Heller, Rita Silmbrod, Nina Zila, Philipp Tschandl, Christoph Hoeller, Anna Sophie Berghoff, Matthias Preusser
Journal: Journal of Clinical Oncology (2023)

9561 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic melanoma with objective response rates of 40-58%. However, reliable biomarkers to predict treatment response are lacking. Tumor tissue methylation profiles were recently proposed to have predictive value in various solid organ tumor entities. Methods: Patients with metastatic melanoma, American Joint Committee on Cancer (AJCC; 8 th Edition) stage IV, receiving first-line ICI-based therapy, were retrospectively identified and formalin-fixed paraffin-embedded tumor tissue samples (FFPE) prior to ICI therapy were retrieved. We analyzed DNA methylation profiles of &gt; 850.000 CpG sites in tumor specimens by Infinium MethylationEPIC microarrays. DNA methylation profiles were then correlated with radiological response (iRECIST). Results: 71 patients with metastatic melanoma (44 (62.0%) male, 27 (38.0%) female) were investigated; median progression free survival (PFS) was 8.5 months (range: 0 – 104.1 months) and median overall survival (OS) was 30.6 months (range: 0 – 104.1 months), respectively. 29 (40.8%) patients achieved an objective response to ICIs. Microarray analyses revealed a methylation signature including mainly hypomethylation, corresponding to the response to ICIs. Based on the 500 mostly differentially methylated genes, a total of 3 clusters were identified with the majority of responders being in cluster 2 (12/12) and 3 (12/22). The predictive performance of the methylation signature was high with 80% sensitivity, 81% specificity, and an AUC of 0.853. Conclusions: Our findings suggest that tumor DNA methylation profiling may be useful to predict response to ICIs in patients with metastatic melanoma.
Gaps and factors in patient awareness of biomarker test timing and purpose in non-small cell lung cancer (NSCLC): Baseline assessment for implementation of 4R Oncology model.
Authors: Nisha Anjali Mohindra, Julia R. Trosman, Stefanie Houseknecht, Josephine Louella Feliciano, Ruth Lauren Sacks, Joan E. Cain, Benjamin Souter, Wendi Waugh, Jennifer Woodyard, Jeremiah Martin, Laura Schmidt, Cara Chang, Anna Rediske, Sonia Zavala, Thomas William Lycan, Nikki A. Martin, Leigh Boehmer, Elana Plotkin, Ashley Lile, Christine B. Weldon
Journal: Journal of Clinical Oncology (2023)

e21059 Background: Biomarker testing is necessary for optimal 1 st line treatment selection in advanced NSCLC. Patient understanding of timing and purpose of biomarker testing is imperative for patient engagement in care, but is challenging to achieve (Martin Oncol Issues 2022). The 4R Oncology model of patient self-management and timely care delivery has been shown to improve patient knowledge of timing/sequence of care in breast cancer (Trosman JCOOP 2021) but has not been studied in NCLSC in relation to biomarker testing. 4R is being implemented at 5 centers (3 community and 2 academic) in NSCLC. We report baseline assessment of patient awareness of biomarker testing timing and purpose to inform 4R implementation. Methods: Pre-implementation surveys of patients with advanced NSCLC at 5 centers Aug – Dec 2022. Metrics are listed in Table. Results: Survey response rate: 46% (65/142). Respondents were 65% white, 42% high school educated or less, 46% with annual income ≤$30K. While all patients were aware of receiving non-biomarker tests, &gt; 40% were not aware of receiving biomarker testing (Table). About half knew why or how long they needed to wait for results, but only 29% received this information from providers. Of those tested, the majority reported provider discussions of biomarkers or therapy selection and were clear about results or therapy selection. Awareness (eg knowing to wait for results before therapy) was associated with receiving printed NSCLC materials (45% vs 7%, p &lt; .01), education above high school (69% vs 41%, p = .03) and income &gt; $30K (67% vs 32%, p = .01). Willingness to wait for test results was associated with knowing how to prepare for treatment while waiting (89% vs 46%, p &lt; .01). Race did not impact these metrics. Conclusions: Considerable gaps exist in patient awareness of timing and purpose of biomarker testing. We refined the 4R model to emphasize biomarker timing in printed visual material, facilitate patient-provider discussions and engage patients in health maintenance while waiting for results. We revised 4R to a lower literacy level. Results will be reported when available. [Table: see text]
Analysis of hospitalizations of patients with Kaposi sarcoma: A national population-based study.
Authors: Philip Onyekaoso Kanemo, Ayobami Gbenga Olafimihan, Ted Akhiwu, Ehizogie Edigin, Muhammad Bilal Ibrahim, Anthonia Ijeli, Osaigbokan Aihie, Dan Ran Castillo, Muhammad Nauman Riaz
Journal: Journal of Clinical Oncology (2023)

e18821 Background: Kaposi sarcoma (KS) is a type of soft tissue sarcoma due to infection with human herpes virus 8 (HHV-8) and can be associated with acquired immunodeficiency syndrome [AIDS]. Recent national population data are scarce on reasons for hospitalizations, epidemiology, and hospitalization outcomes of patients with KS in the United States (U.S). Methods: Data were abstracted from the National Inpatient Sample (NIS) Database. This database is the largest collection of inpatient admission data in the U.S. It is a 20-percent stratified sample of all discharges from U.S. community hospitals, excluding rehabilitation and long-term acute care hospitals. The numbers in the databases are weighted to optimize national estimates. Hospitalizations for patients with KS were obtained by searching for hospitalizations that contained ICD-10 code “C46” as a principal or secondary diagnosis. The principal diagnosis is the main reason for the admission, while any other diagnosis other than the principal, are secondary diagnosis. The reason for hospitalization (or principal diagnosis) was recorded in descending order of frequency based on the ICD-10 code organ system category and specific principal diagnosis. The total number of KS discharges, baseline demographic characteristics, hospital length of stay (LOS), and total hospital charges were recorded. STATA 16 was used for analysis. Since NIS contains de-identified data, Institutional Review Board (IRB) review was waived. Results: There were 32 million discharges included in the 2020 NIS database. Of those, 2,785 hospitalizations were for patients aged ≥18 years, who had either a principal or secondary ICD 10 code for KS. Patients were mainly males (91%), black (40%), mean age of 48 years, inpatient mortality of 9.3%, mean LOS of 9 days, and mean total hospital charge of 132,476 U.S dollars. The 5 most common reasons for hospitalization by ICD 10 code categories were infections (52.4%), cardiovascular (6.5%), respiratory (6.1%), neoplasm and hematologic (5.6%), and skin (5.6%). The 5 most common specific principal diagnoses for hospitalizations were Human immunodeficiency virus [HIV] disease (29.1%), sepsis (12.7%), left leg cellulitis (2.7%), pneumonia (2.2%), and Acute kidney injury (1.8%). Conclusions: Hospitalizations for KS patients are mostly black middle-aged men, with high inpatient mortality, long LOS, and significant hospital charges. Infections and HIV were the most common reasons for hospitalizations. Management of underlying HIV and measures for prevention, early detection, and prompt treatment of infections in the outpatient setting are important in preventing hospitalizations of these patients.
How does the war affect breast cancer quality of care? The Syrian experience.
Authors: Fouad Nahhat, Firas Benyamine Badin, Maher Saifo
Journal: Journal of Clinical Oncology (2023)

e18724 Background: The Syrian decade-long war has severely affected the healthcare system, including almost vanishing cancer screening practices, war-destroyed medical facilities, and lack of continuous medical education. This study aims to present data on the affected breast cancer screening practices, methods of diagnosis, and stages distribution in Syria. Methods: Medical records of breast cancer patients treated at Albairouni University Hospital between 2019 and 2022 were retrospectively reviewed. Eligible patients were women diagnosed with primary breast cancer. Exclusion criteria included male gender, females receiving neoadjuvant chemotherapy, and incomplete charts. Data regarding the patient's age, city of residence, marital status, number of children, smoking habits, method of diagnosis, tumor size (T), lymph nodes (N), and distal metastasis (M) were collected. We used Microsoft Excel and Statistical Package for the Social Sciences (SPSS) to analyze data. Descriptive methodology (frequency [n], percentage) was used. Results: The number of included patients after applying the exclusion criteria was 2,367. The mean age was 51.8 (SD = 11.3). More than half of the patients (58.3%) came from outside Damascus -where the hospital is located- and its suburbs. Less than 5% of the population detected cancer by screening mammography. Only 32.4% of patients were diagnosed by a biopsy, while surgical procedures were used to diagnose 64.8% of the population. At the time of diagnosis, only 8% of patients presented with local-stage disease (stages 0 &amp; I), 73% had a regional disease (stages II &amp; III), and 19% had metastatic breast cancer (stage IV). Conclusions: Our retrospective chart review analysis is the first comprehensive review in Syria for female breast cancer patients. We found a chocking low percentage of patients diagnosed based on a screening mammogram, much higher surgical biopsies rather than a simple imaging-guided biopsy, and much lower than the national average of early-stage disease. Factors that might explain our results include lack of appropriate education, restricted access to medical facilities, and financial restraints. Our alarming findings can serve as the base for future strategies to improve breast cancer care in Syria by detecting the disease earlier and avoiding surgical diagnostic procedures.
Randomized phase 3 study of first-line AZD3759 (zorifertinib) versus gefitinib or erlotinib in EGFR-mutant (<i>EGFR</i>m<sup>+</sup>) non–small-cell lung cancer (NSCLC) with central nervous system (CNS) metastasis.
Authors: Yi-Long Wu, Qing Zhou, Jie Wang, Yan Yu, Ligang Xing, Ying Wang, Ying Cheng, Yueyin Pan, Yun Fan, Jianhua Shi, Guojun Zhang, Jiuwei Cui, Jianying Zhou, Yong Song, Wu Zhuang, Zhiyong Ma, Yanping Hu, Gaofeng Li, Xiaorong Dong, Myung-Ju Ahn
Journal: Journal of Clinical Oncology (2023)

9001 Background: Patients (pts) with EGFRm + NSCLC have high rates of CNS metastasis, few treatment options, and a poor prognosis. So far there are no solid evidence from head to head phase 3 trials in this setting. The potent EGFR TKI AZD3759 has high blood–brain barrier penetration, preliminary data has shown promising intracranial (IC) and systemic antitumor activity, and a tolerable safety profile. Methods: This was the first phase 3, open-label, multicenter, randomized controlled trial to compare the efficacy and safety of first-line AZD3759 with first generation EGFR TKIs specifically in pts with EGFRm + (L858R and/or exon 19Del) NSCLC and CNS metastasis. Adult pts were randomized 1:1 to receive AZD3759 (200 mg twice daily) or first generation EGFR TKIs (the control group, gefitinib 250 mg or erlotinib 150 mg once daily). The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1. Results: Between Feb 1, 2019, and Jan 12, 2021, 439 pts were randomized: 220 to AZD3759 and 219 to the control group. As of July 12, 2022, median follow-up was 20.4 months (mo) for both. Median PFS (95% CI) was significantly superior with AZD3759 vs the control group (9.6 [8.2–9.7] vs 6.9 [6.3–8.0] mo; HR 0.719, 95% CI 0.580–0.893; p=0.0024). The objective response rate (ORR; BICR/RECIST 1.1) was 68.6% for AZD3759 vs 58.4% for the control group ( p=0.027), with a trend toward longer median duration of response (DoR) with AZD3759 (8.2 vs 6.8 mo; p=0.0997). IC PFS, ORR, and DoR with AZD3759 were all superior vs the control group regardless of the assessor or evaluation criteria. The overall survival was immature. The incidence of any-grade treatment-related adverse events (TRAEs) was similar between the two groups (97.7% vs 94.0%). Grade ≥3 TRAEs occurred in 65.9% (AZD3759) and 18.3% (the control group) of pts. The main TRAEs were skin and subcutaneous tissue events, gastrointestinal system events and abnormal liver function. No new safety signals arose. Conclusions: First-line AZD3759 demonstrated superior systemic and IC antitumor efficacy compared with first generation EGFR TKIs in pts with EGFRm + NSCLC and CNS metastasis. Adverse events were as expected and manageable. IC antitumor activity. Clinical trial information: NCT03653546 . [Table: see text]
Influence of increase in hospital costs on mortality for pleural mesothelioma in teaching hospitals: A nationwide analysis.
Authors: Nehemias Guevara, Garry Francis-Morel, Esmirna Perez, Jean Gabriel Bustamante Alvarez
Journal: Journal of Clinical Oncology (2023)

e20533 Background: Rural and non-teaching hospitals are known to have a lower budget compared to urban-teaching hospitals. Pleural mesothelioma is an aggressive and rare malignancy, and it remains unknown whether treatment in institutions with higher revenue or reimbursement rates impacts outcomes. This study sought to elucidate if such a difference in outcomes exists. Methods: A retrospective cohort analysis of adults admitted from 2016 to 2020 with the primary diagnosis of pleural mesothelioma was conducted. Data was extracted from the National Inpatient Sample Database. We compared outcomes such as mortality, length of stay (LoS), and total charges in teaching versus non-teaching hospitals. Results: We identified 7,320 patients that met inclusion criteria; 84% were admitted to teaching hospitals, and the remaining 16% to non-teaching facilities ( p &lt; 0.001). Elderly patients were the most afflicted group, with a mean age of 72 to 74 years ( p 0.009). No differences in sex, race, or primary insurance distribution were noted ( p 0.067; p 0.731; p 0.801, respectively). The mean hospital LoS was 6.4 days in non-teaching hospitals compared to 7.7 days in teaching hospitals ( p 0.0061). In addition, Asians ( p 0.016), those with a median household income of 65,000 to 85,999 ( p 0.021), higher Charlson index ( p &lt; 0.001), and those admitted to large to medium size hospitals ( p 0.011; p 0.001, respectively) had a positive linear relation to LoS. Moreover, total hospital charges were greater in teaching hospitals (120,100 USD) in comparison to non-teaching hospitals (73,883 USD) ( p &lt; 0.001). Mortality did not differ based on teaching status ( p 0.643). However, Native Americans and those with higher Charlson comorbidity index were more likely to die ( aOR 21, p 0.004; aOR 1.32, p &lt; 0.001, respectively). Conclusions: Hospital teaching status does not impact mortality in patients admitted with malignant pleural mesothelioma, even though teaching hospitals incur higher expenses on average. It does not come as a surprise due to this condition's known high mortality rate, late presentation in advanced stages, and resistance to current therapies. Prevention is key in a deadly disease, and more research is needed to offer a better prognosis; even though current regimens have shown improvement in survival, curative therapies are still unavailable. Even though asbestos is subject to strict regulations in the United States, it is not banned. We should revisit the idea of a complete ban; those most affected tend to have the least access to healthcare and need a safer work environment. Decreasing exposure to known carcinogens should also be a priority, as there is no better medicine than preventive medicine. Interestingly, mortality was greater in Native Americans compared to other races; the underlying causes are broad and need more research and better characterization of MM.